Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CSP1 > Myeloproliferative Syndromes > Flashcards

Myeloproliferative Syndromes Flashcards

1
Q

How do platelets form?

A
  • HSC
  • myeloid progenitor cell
  • megakaryocyte
  • megakaryoblast
  • promegakaryoblast
  • megakaryocyte
  • platelets
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How do RBCs form?

A
  • HSC
  • myeloid progenitor cell
  • erythroid progenitor
  • proerythroblast
  • erythroblast
  • reticulocyte
  • RBCs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How do mast cells form?

A

Directly from common myeloid progenitor cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the main MPN?

A
  • chronic myelogenous leukaemia
  • polycythemia vera
  • essential thrombocytopenia
  • primary myelofibrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What type of genetic conditions are MNP?

A

Acquired

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the characteristics of CML?

A
  • uncontrolled mature granulocytic proliferation
  • 9,22 Philadelphia chromosome present
  • long chromosome 9 and short 22
  • men more common
  • 50 years common
  • increased granulocytes in all stages of maturation unlike acute which are all mature blasts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Presentation of CML

A 
Systemic
- fatigue
- night sweats
- malaise
- weight loss
Splenomegaly
- early satiety
- L. upper quadrant pain
Hyper viscosity
- headache/blurred vision
- fluid overload
- thrombosis and haemorrhage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

When can CML become AML?

A

in the blast phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Diagnosis of CML?

A
  • raised WCC
  • basophilia
  • blood film
  • bone marrow biopsy
  • G banding
  • FISH
  • Reverse transcriptase PCR (quantitative, telling you how many BCR-ABL)
  • Low NAP/LAP score (alkaline phosphatase score)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the hallmark of chronic myeloid leukaemia?

A

Philadelphia chromosome

  • also occurs in AML
  • shortened chromosome 22 and longer 9
  • due to translocation
  • causes fusion of BCR and ABL genes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does BCR-ABL code for?

A
  • encodes tyrosine kinase which becomes constitutively active = uncontrolled cell division and inhibits DNA repair = genetic instability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How is CML treated?

A
  • imatinib (1st generation) and 2nd/3rd generation TKIs
  • some don’t respond so chemotherapy or if progressed to AML
  • cure with allogeneic HSC transplant sometimes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Prognosis of CML?

A
  • increased LE

- good

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is primary polycythaemia vera?

A
  • increased RBC volume as clonal malignancy of marrow stem cell
  • all 3 cell lines can be increased (white and platelets)
  • otherwise unexplained high haematocrit so need to rule out other causes
  • usually from JAK2 mutation
  • age 60 common
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the significance of haematocrit in polycythaemia vera?

A
  • % of total blood volume is made from RBCs
  • normal is 55%
  • raised in PV due to increased RBC volume only
  • increased by increased RBC or reduced plasma due to dehydration so need to rule this out
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Requirements for polycythaemia vera diagnosis?

A

Increase in haematocrit due to increase in % of RBC volume

  • males > 0.6
  • females > 0.56

raised for more 2 months

Hb > 18.5 in males and 16.5 in females

17
Q

Other causes of raised haematocrit/polycythaemia

A

Relative = apparent/reduced plasma volume due to dehydration

True = absolute due to increase in RBC

  • can be true primary where EPO is low or normal= PV
  • true secondary is overproduction of EPO
18
Q

Causes of true secondary polycythaemia

A 
Hypoxic driven
- high altitude
- cardiopulmonary disease
- defective oxygen transport
Hypoxia independent
- renal cysts/ tumours
- extrarenal tumors
- exogenous EPO/drugs
19
Q

Presentation of polycythaemia vera

A
  • asymptomatic for many
  • plethoric appearance (red)!
  • post bath puritis (aquagenic puritis)!
  • splenomegaly
  • acute gout
  • headache
  • erythromelalgia (occlusion of vessels in fingers)
  • thrombosis !
  • haemorrhage
20
Q

Diagnosis of PV (stage 1)

A
  • history
  • examination
  • FBC (elevated Hb and Hc o no other cause)
  • ferritin will be low as making lots of RBCs so iron deficiency
  • JAK2 mutation for definitive test
  • renal and liver function
21
Q

Why don’t you give iron in PV?

A

Will make even more RBCs which don’t need

May mask erythrocytosis

22
Q

What is the role of JAK2 in PV?

A
  • intracellular protein and TKR
  • attached to EPO receptor
  • EPO binds to receptor activating JAK2
  • activates JAK2 IC pathway
  • allows proliferation and survival of cell to make more RBC
  • if mutated = constitutively active protein so uncontrolled RBC proliferation
23
Q

Diagnosis of PV (stage 2)

A
  • Low serum EPO
  • arterial SO2 to look for 2ndry causes
  • abdom US for splenomegaly or renal tumour
  • bone marrow biopsy
  • red cell mass study (determines true or relative erythrocytosis)
24
Q

Prognosis of PV

A 
10-16 years survival 
Cardiovasc events
Thrombosis
Progression to myelofibrosis
Progression to AML like all MPNs
2ndry haemorrhage in all MPNs
25
Q

Treatment of PV?

A
  • venesection is HCT <0.45
  • aspirin
  • myelosuppressive drugs (hydroxycarbamide, interferon, busulphan)
  • JAK inhibitors
26
Q

What is essential thrombocythaemia

A
  • sustained increase in platelet count as megakaryocytic proliferation
  • define by ruling out all other causes of raised platelet count
  • not morphologically or cytogenetically defined
  • more common in females
  • 60 years
  • overall good survival 10 years
27
Q

Presentation of thrombocythaemia

A
  • asymptomatic mainly
  • thrombosis arterial and venous
  • haemorrhage as poor platelet function
  • erythromelalgia
  • splenomegaly
  • fatigue/malaise/weight loss
28
Q

What are secondary causes of raised platelet count?

A
  • chronic infection
  • chronic inflammation
  • iron deficiency
  • haemorrhage response
  • hyposplenism
  • malignancy
  • drugs (steroids)
  • exclude other myeloid malignancy
29
Q

How to diagnose thrombocythemia?

A
  • JAK2 mutation common
  • CALR and MPL mutations sometimes
  • bone marrow biopsy = elevated megakaryocytes
30
Q

Prognosis of thrombocythemia

A
  • 10 year survival
  • risk of thrombosis and bleeding
  • transformation MF and AML
31
Q

Treatment of thrombocythemia

A
  • all patients on aspirin

- myelosuppressive drugs (hydroxycarbamide - especially if thrombosis before to normalise platelet count)

32
Q

Why are venesections not practical for thrombocythemia?

A

platelets life is only 7-10 days so will have to keep doing them

33
Q

What is myelofibrosis?

A
  • clonal stem cell malignancy
  • primary = on its own
  • secondary = progression from other MPN
  • bone marrow replaced by scar tissue (fibrosis) which is stimulated by abnormal megakaryocytes
  • untreated -> raise in blood count initially but then eventually drop -> AML eventually
  • JAK2 common, CALR, MPL
34
Q

Presentation of myelofibrosis

A
  • fatigue
  • weight loss
  • night sweats
  • raised WCC initially then drop
  • progressive cytopenias
  • massive splenomegaly
  • extramedullary haematopoiesis as spleen takes over making it massive
35
Q

Characteristic of myelofibrosis blood film

A
  • teardrop poikilocytes (abnormal shape) and leucoerythroblastic (white and nucleated red blasts)
36
Q

Bone marrow biopsy in myelofibrosis

A
  • increase in fibrosis so increased reticulin
  • streaming (architecture disrupted)
  • increased cellularity
37
Q

Diagnosis of myelofibrosis

A
  • bone marrow reticulin fibrosis
  • splenomegaly
  • anaemia
  • teardrop poikilocytes and leucoerythroblastic blood film
  • JAK2 mutation, CALR, MPL
38
Q

Treatment of myelofibrosis

A
  • dependent on risk
  • poor prognosis as AML progression risk
  • stratify risk based on age and blast count
  • transfusion for supportive management
  • splenectomy
  • if high risk = allogeneic SC transplant
  • JAK inhibitors (ruxolitinib)
  • hydroxycarbamide control high cell counts
  • andorgens (anabolic steroids stimulate bone marrow improving low bloow count)
39
Q

Prognosis of myelofibrosis

A
  • poor overall
  • 1 year survival if high risk
  • 12 years if low risk
  • risk factors = age, blast, transfusion dependence, cytogenetics
  • progression to AML being main reason

CSP1 (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions